The main objective of this proposal is to determine whether the handling and disposition of cholesterol in adult life can be influenced by perturbation of cholesterol degradation and synthesis at the neonatal stage. Cholesterol homeostases in the neonatal guinea pigs would be perturbed as follows: (a) enhancement of cholesterol degradation (cholestyramine), (b) early exposure to high dietary cholesterol, (c) minimum exposure to cholesterol of intestinal origin (beta-sitosterol feeding with low cholesterol diet), and (d) preweaning. The effect on these early manipulations on the following parameters of sterol metabolism would be examined subsequently: (a) plasma cholesterol concentrations, (b) cholesterol absorption, (c) bile acids and neutral sterol excretion, (d) bile acid pool, and (e) hepatic rate-limiting enzyme of cholesterol synthesis and degradation. The effect of age, duration, and sex differences in response to perturbation will also be examined. The long-term effects of these perturbations on the cholesterol homeostasis in the adults would also be determined by subjecting the animals to dietary cholesterol challenge and observing their response in terms of the above-mentioned parameters. These experiments should furnish important information on the potential neonatal maneuvers capable of altering cholesterol homeostasis in the adult. This information is critical in recommendations concerning pediatric approaches to the control of cardiovascular diseases in man.